Tetrahydrofuran → HCID 57420351, compound

HRID 1842313Notes

Reaction equation

HRID 1842313 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=O)[CH2:15][O:16][CH3:17])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]([Mg]Br)[CH3:20].[CH2:23]1COC[CH2:24]1>C(Cl)(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2([CH2:15][O:16][CH3:17])[CH2:20][CH2:19]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([CH2:19][CH3:20])([CH2:15][O:16][CH3:17])[CH2:23][CH3:24])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 1122381HCID 1122381, compoundHCID 178418443HCID 178418443, compound

Product 2

HCID 57420351HCID 57420351, compoundHCID 57449816HCID 57449816, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6212ChloroformSolvent

Procedure

To a solution of 1-(4-benzyl-piperazin-1-yl)-2-methoxy-ethanone (2.60 g) in dry THF (30 mL) at −10° C. was added titanium isopropoxide (3.22 mL), followed by ethyl magnesium bromide (1.0M solution in THF, 22.05 mL). The reaction mixture was heated to reflux for 2 days. After cooling the reaction mixture was cooled, diluted with chloroform, washed with brine, dried (MgSO4) and the solvent removed in vacuo. The residue was purified using flash chromatography to yield 1-benzyl-4-(1-methoxymethyl-cyclopropyl)-piperazine (452 mg) and 1-benzyl-4-(1-ethyl-1-methoxymethyl-propyl)-piperazine (248 mg). Transfer hydrogenation conditions using ammonium formate and 10% Pd/C in MeOH afforded the desired compound.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 days
  3. temperatureAfter cooling the reaction mixture
  4. temperaturewas cooled
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed in vacuo
  8. customThe residue was purified

Sources & evidence

ORD record
ord-f5cc8b1234d4420296434253d57f841b
Source dataset
uspto-grants-2015_02
Patent number
US08946217B2

Reaction notes

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